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Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Wu, Yee Ling 
Stubbington, Michael JT  ORCID logo  https://orcid.org/0000-0001-5924-3566
Teichmann, Sarah A 

Abstract

Noncoding transcripts originating upstream of the immunoglobulin constant region (I transcripts) are required to direct activation-induced deaminase to initiate class switching in B cells. Differential regulation of Iε and Iγ1 transcription in response to interleukin 4 (IL-4), hence class switching to IgE and IgG1, is not fully understood. In this study, we combine novel mouse reporters and single-cell RNA sequencing to reveal the heterogeneity in IL-4-induced I transcription. We identify an early population of cells expressing Iε but not Iγ1 and demonstrate that early Iε transcription leads to switching to IgE and occurs at lower activation levels than Iγ1. Our results reveal how probabilistic transcription with a lower activation threshold for Iε directs the early choice of IgE versus IgG1, a key physiological response against parasitic infestations and a mediator of allergy and asthma.

Description

Keywords

Animals, B-Lymphocytes, Cytidine Deaminase, Immunoglobulin Class Switching, Immunoglobulin E, Interleukin-4, Mice, Mice, Inbred BALB C, Promoter Regions, Genetic, Transcription, Genetic

Journal Title

J Exp Med

Conference Name

Journal ISSN

0022-1007
1540-9538

Volume Title

214

Publisher

Rockefeller University Press

Rights

Publisher's own licence